acceleration of ketogenesis in the liver (G. A. H. Johnson & K. G. M. M. Alberti, unpublished work). Fructose injection into galactosamine-treated rats resulted in a marked increase in blood lactate concentration (Table I), an increase in blood glucose concentration (Table 2) and a dramatic decrease in blood ketone-body concentrations (Table 2) when compared with galactosamine-treated control r...

Pyruvate has been shown to both stimulate and inhibit kidney pyruvate dehydrogenase, (PDH,) kinase activity. The present study investigates the inhibitory effect of pyruvate under conditions in which the stimulatory effect is invariant. Inhibition of PDH, kinase activity by dichloroacetate, a pyruvate analog, is also characterized. Both pyruvate and dichloroacetate are uncompetitive, hyperbolic...

Pyruvate has been shown to both stimulate and inhibit kidney pyruvate dehydrogenase, (PDH,) kinase activity. The present study investigates the inhibitory effect of pyruvate under conditions in which the stimulatory effect is invariant. Inhibition of PDH, kinase activity by dichloroacetate, a pyruvate analog, is also characterized. Both pyruvate and dichloroacetate are uncompetitive, hyperbolic...

1. Sodium dichloroacetate (1mM) inhibited glucose production from L-lactate in kidney-cortex slices from fed, starved or alloxan-diabetic rates. In general gluconeogenesis from other substrates was no inhibited. 2. Sodium dichloracetate inhibited glucose production from L-lactate but no from pyruvate in perfused isolated kidneys from normal or alloxan-diabetic rats. 3. Sodium dichloroacetate is...

1. Sodium dichloroacetate (300mg/kg body wt. per h) was infused in 24h-starved rats for 4h. 2. Blood glucose decreased significantly, an effect that had previously only been noted in diabetic animals 3. Plasma insulin concentration decreased by 63%; blood lactate and pyruvate concentrations decreased by 50 and 33%, whereas concentrations of 3-hydroxybutyrate and acetoacetate increased by 81 and...

The use of dichloroacetate (DCA) for treating patients with mitochondrial diseases is limited by the induction of peripheral neuropathy. The mechanisms of DCA-induced neuropathy are not known. Oral DCA treatment (50-500 mg/kg per day for up to 16 weeks) induced tactile allodynia in both juvenile and adult rats; concurrent thermal hypoalgesia developed at higher doses. Both juvenile and adult ra...

1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in perfused rat heart was decreased by alloxan-diabetes or by perfusion with media containing acetate, n-octanoate or palmitate. The total activity, of the dehydrogenase was unchanged. 2. Pyruvate (5 or 25mm) or dichloroacetate (1m) increased the proption of active (dephosphorylated) pyruvate debydrogenase in perfused rat hea...

Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progr...